⁶⁸Ga-labeled prostate-specific membrane antigen (⁶⁸Ga-PSMA) PET/CT has a proven role in staging and restaging of prostate cancer (PCA). The aims of this study were to evaluate the association of intraprostatic ⁶⁸Ga-PSMA PET/CT findings and PSMA expression in immunohistochemical staining and generate a cutoff value for differentiation between normal prostate (PN) and PCA. Methods: The data of 31 patients (mean age, 67.2 y) who underwent prostatectomy and preoperative PET were retrospectively analyzed. On PET, focally increased uptake in the prostate was suggestive of tumor. A region of interest was placed on the suggestive area to generate an SUV_max; a similar region of interest was placed on adjacent visually PN. Both PCA and PN were stained with monoclonal anti-PSMA antibody (clone 3E6, 1:100, M3620). Results: All intraprostatic PCA lesions on PET could be confirmed histopathologically. In PN sections (n = 31), median staining intensity was mild, median percentage of stained cells was 20% ± 14.24%, and median immunoreactive score (IRS) was 1. In PCA sections (n = 31), median IRS was 3, median staining intensity was strong, and median percentage of stained cells was 80% ± 16.46%. The mean SUV_max (±SD) of PCA (14.06 ± 15.56) was significantly higher than that of PN (2.43 ± 0.63; P < 0.001). Receiver-operating-characteristic curve analyses of the SUV_max of PCA, validated by immunohistochemical staining in 62 tissue samples, showed the best cutoff to be 3.15 (sensitivity, 97%; specificity, 90%; area under curve, 0.987). Applied to multifocal PCA, it resulted in sensitivity and specificity of 87% and 97% respectively. The mean SUV_max of PCA and PN for an IRS of less than 2 (n = 26; 2.52 ± 0.64) was significantly lower than the mean SUV_max for an IRS of 2 or more (n = 36; 12.38 ± 15.02; P < 0.001). The mean SUV_max was significantly lower in PCA samples with fewer than 50% stained cells (n = 30; 2.81 ± 2.35) than in samples with 50% or more (n = 32; 13.34 ± 15.55; P < 0.001). There was no correlation between the SUV_max of PCA and Gleason score (P = 0.54). Conclusion: This study showed that SUV_max on ⁶⁸Ga-PSMA PET/CT correlates significantly with PSMA expression in primary PCA, enabling the detection of PCA with a high sensitivity and specificity.

Radioligand therapy (RLT) is considered a safe treatment for patients with metastasized neuroendocrine tumors (NET) and prostate cancer (PC), and the occurrence of tumor lysis syndrome (TLS) with ¹⁷⁷Lutetium (¹⁷⁷Lu)-labeled peptides has not been reported so far. We retrospectively screened our patients’ database for TLS after RLT in NET and PC. Methods: The database was searched for patients receiving RLT with ¹⁷⁷Lu-DOTATATE, -DOTATOC or -PSMA and showing laboratory or clinical abnormalities typical for TLS within 7 days after start of treatment. Results: 205 patients (539 cycles) were screened; 4 patients developed TLS with clinical symptoms and characteristic changes of laboratory parameters, which normalized after appropriate treatment. Follow-up revealed partial remission (n = 2), mixed response (n = 1) and progressive disease (n = 1). Conclusion: Clinical TLS is a rare, but definite complication of RLT suggesting patient monitoring for TLS as mandatory.

Aim: The most suitable method for assessment of response to peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NET) is still under debate. In this study we aimed to compare size (RECIST 1.1), density (Choi), Standardized Uptake Value (SUV) and a newly defined ZP combined parameter derived from Somatostatin Receptor (SSR) PET/CT for prediction of both response to PRRT and overall survival (OS). Material and Methods: Thirty-four NET patients with progressive disease (F:M 23:11; mean age 61.2 y; SD ± 12) treated with PRRT using either Lu-177 DOTATOC or Lu-177 DOTATATE and imaged with Ga-68 SSR PET/CT approximately 10–12 weeks prior to and after each treatment cycle were retrospectively analyzed. Median duration of follow-up after the first cycle was 63.9 months (range 6.2–86.2). A total of 77 lesions (2–8 per patient) were analyzed. Response assessment was performed according to RECIST 1.1, Choi and modified EORTC (MORE) criteria. In addition, a new parameter named ZP, the product of Hounsfield unit (HU) and SUVmean (Standard Uptake Value) of a tumor lesion, was tested. Further, SUV values (max and mean) of the tumor were normalized to SUV of normal liver parenchyma. Tumor response was defined as CR, PR, or SD. Gold standard for comparison of baseline parameters for prediction of response of individual target lesions to PRRT was change in size of lesions according to RECIST 1.1. For prediction of overall survival, the response after the first and second PRRT were tested. Results: Based on RECIST 1.1, Choi, MORE, and ZP, 85.3%, 64.7%, 61.8%, and 70.6% achieved a response whereas 14.7%, 35.3%, 38.2%, and 29.4% demonstrated PD (progressive disease), respectively. Baseline ZP and ZPnormalized were found to be the only parameters predictive of lesion progression after three PRRT cycles (AUC ZP 0.753; 95% CI 0.6–0.9, p 0.037; AUC ZPnormalized 0.766; 95% CI 0.6–0.9; p 0.029). Based on a cut-off-value of 1201, ZP achieved a sensitivity of 86% and a specificity of 67%, while ZPnormalized reached a sensitivity of 86% and a specificity of 76% at a cut-off-value of 198. Median OS in the total cohort was not reached. In univariate analysis amongst all parameters, only patients having progressive disease according to MORE after the second cycle of PRRT were found to have significantly shorter overall survival (median OS in objective responders not reached, in PD 29.2 months; p 0.015). Patients progressive after two cycles of PRRT according to ZP had shorter OS compared to those responding (median OS for responders not reached, for PD 47.2 months, p 0.066). Conclusions: In this explorative study, we showed that Choi, RECIST 1.1, and SUVmax-based response evaluation varied significantly from each other. Only patients showing progressive disease after two PRRT cycles according to MORE criteria had a worse prognosis while baseline ZP and ZPnormalized performed best in predicting lesion progression after three cycles of PRRT.

Background: The De Ritis ratio (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) has demonstrated prognostic value in various cancer entities. We evaluated the prognostic capability of the De Ritis ratio in patients with metastatic neuroendocrine tumors (NET) undergoing peptide receptor radionuclide therapy (PRRT). Methods: Unicentric, retrospective analysis of 125 patients with NET undergoing PRRT with [¹⁷⁷Lu]Lu-DOTATOC (female: 37%; median age: 66 years; G1+G2 NET: 95%). The prognostic value regarding progression-free survival (PFS) was analyzed with univariable and multivariable Cox regression. Prognostic accuracy was determined with Harrell’s C index and a likelihood ratio test. Results: Progression, relapse, or death after PRRT was observed in 102/125 patients. Median progression-free survival (PFS) was 15.8 months. Pancreatic or pulmonary origin, high De Ritis ratio, and high Chromogranin A (CgA) significantly predicted shorter PFS in univariable Cox. In multivariable Cox regression, only high De Ritis ratio >0.927 (HR: 1.7; p = 0.047) and high CgA >twice the upper normal limit (HR: 2.1; p = 0.005) remained independent predictors of shorter PFS. Adding the De Ritis ratio to the multivariable Cox model (age, Eastern Cooperative Oncology Group (ECOG) performance status, primary origin, CgA) significantly improved prognostic accuracy (p < 0.001). Conclusions: The De Ritis ratio is simple to obtain in clinical routine and can provide independent prognostic value for PFS in patients with NET undergoing PRRT.

Neck management in patients with early-stage, clinically node-negative oral squamous cell carcinoma (OSCC) remains a matter of discussion. Sentinel lymph node biopsy (SLNB) represents a treatment alternative to avoid elective neck dissection (END) in this cohort and different protocols and tracers exist. Here we present the clinical outcome of SLNB using ^99mTc-tilmanocept in a two-day protocol in patients suffering from early-stage OSCC. A total of 13 patients (males: 6; females: 7; mean age: 65.7 years, ranging from 47 to 89 years) were included in this study. Most of the patients suffered from an OSCC of the floor of mouth (n = 6), followed by tongue (n = 5) and upper alveolar crest/hard palate (n = 2). Sentinel lymph nodes (SLNs) were successfully identified in all cases (range: 1–7). The average length of hospital stay was 4.7 days (range: 3–8 days) and mean duration of surgical intervention was 121 min (range: 74–233 min). One patient who suffered from an OSCC of the tongue was sentinel lymph node positive (SLN+). The mean follow-up for all sentinel lymph node negative (SLN-) patients (n = 12) was 20.3 months (range: 10–28 months). No local or nodal recurrences were observed within the observation period. In our patient cohort, SLNB using ^99mTc-tilmanocept in a two-day protocol proved to be a reliable and safe staging method for patients suffering from early-stage, clinically node-negative OSCC. These results and their possible superiority to colloid tracers have to be confirmed in a prospective randomized controlled study.